colorectal cancer research

Colorectal cancer (CRC) progression is fueled by immunosuppressive crosstalk within the tumor microenvironment. Through integrated single-cell and bulk transcriptomic analyses, we identify MIF signaling as the dominant pathway governing tumor epithelium-B cell interactions. Subcluster profiling revealed MIF-(CD74+CXCR4/CD44) drives communication from malignant cells to Naive/Exhausted B cells. Pathway refinement via ComPath pinpointed MIF-CD74 as the core interaction hub, triggering PAX5-dependent suppression of the tumor suppressor DMTF1 in B cells. Multi-cohort validation confirmed strong PAX5-Naive B cell correlation and inverse MIF/DMTF1 expression in CRC versus normal tissues. Functional assays demonstrated tumor-derived MIF upregulates CD74/PAX5 and silences DMTF1 in B cells—reversed by MIF blockade. This study establishes the MIF-CD74-PAX5-DMTF1 axis as a novel mechanism of B cell dysfunction in CRC, proposing its therapeutic targeting to reverse immune evasion in microsatellite stable tumors.